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<p>Lactylation is a newly identified post-translational modification that plays a key role in chromatin remodeling and gene regulation. Accumulating evidence implicates aberrant lactylation in cancer progression, neurological and cardiovascular disorders. Traditional Chinese Medicine (TCM), often perceived as having favorable tolerability, is characterized by multi-target actions and metabolic modulatory effects, which together suggest potential relevance for regulating lactylation. Bioactive compounds such as flavonoids, alkaloids, polysaccharides, and ginsenosides have been shown to influence both histone and non-histone lactylation through metabolic rewiring and modulation of lactylation-related proteins and enzymes. This review systematically investigates the role of lactylation in disease progression and evaluates the therapeutic potential of TCM-based interventions across diverse pathological contexts. We systematically delineate four distinct mechanistic layers: upstream lactate control (e.g., fargesin inhibiting PKM2/glycolysis), direct lactylation machinery modulation (e.g., tanshinone I decreasing H3K18la), downstream functional consequences (e.g., evodiamine blocking HIF1α/PD-L1 signaling), and lactylation as a pharmacodynamic biomarker.&#xa0;Thus, linking lactylation with TCM may provide a conceptual framework for developing lactylation-targeted therapeutics and rational combination strategies in precision medicine.</p> Graphical Abstract <p></p>

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Targeting Lactylation with Traditional Chinese Medicine: Unveiling Molecular Mechanisms and Emerging Therapeutic Strategies

  • 期刊论文

  • 发表日期：

    2026年3月23日

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  • Meihui Qin,
  • Song Wu,
  • Anqi Xie,
  • Xiaoyue Huang,
  • Wei Lu,
  • Huanjiao Zhou

摘要

Lactylation is a newly identified post-translational modification that plays a key role in chromatin remodeling and gene regulation. Accumulating evidence implicates aberrant lactylation in cancer progression, neurological and cardiovascular disorders. Traditional Chinese Medicine (TCM), often perceived as having favorable tolerability, is characterized by multi-target actions and metabolic modulatory effects, which together suggest potential relevance for regulating lactylation. Bioactive compounds such as flavonoids, alkaloids, polysaccharides, and ginsenosides have been shown to influence both histone and non-histone lactylation through metabolic rewiring and modulation of lactylation-related proteins and enzymes. This review systematically investigates the role of lactylation in disease progression and evaluates the therapeutic potential of TCM-based interventions across diverse pathological contexts. We systematically delineate four distinct mechanistic layers: upstream lactate control (e.g., fargesin inhibiting PKM2/glycolysis), direct lactylation machinery modulation (e.g., tanshinone I decreasing H3K18la), downstream functional consequences (e.g., evodiamine blocking HIF1α/PD-L1 signaling), and lactylation as a pharmacodynamic biomarker. Thus, linking lactylation with TCM may provide a conceptual framework for developing lactylation-targeted therapeutics and rational combination strategies in precision medicine.

Graphical Abstract